Selective block of late Na+ current by local anaesthetics in rat large sensory neurones

1 The actions of lignocaine and benzocaine on transient and late Na+ current generated by large diameter (greater than or equal to 50 mu m) adult rat dorsal root ganglion neurones, were studied using patch-clamp techniques. 2 Both drugs blocked whole-cell late Na+ current in a concentration-dependent manner. At 200 ms following the onset of a clamp step from -110 to -40 mV, the apparent K for block of late Na+ current by lignocaine was 57.8 +/- 15 mu M (mean +/- s.e.mean, n = 4). The value for benzocaine was 24.9 +/- 3.3 mu M, (mean +/- s.e.mean, n = 3). 3 The effect of lignocaine on transient current, in randomly selected neurones, appeared variable (n = 8, half-block from similar to 50 to 400 mu M). Half-block by benzocaine was not attained, but both whole-cell (n = 11) and patch data suggested a high apparent K-i>250 mu M. Transient current always remained after late current was blocked. 4 The voltage-dependence of residual late current steady-state inactivation was not shifted by 20 mu M benzocaine (n = 3), whereas 200 mu M benzocaine shifted the voltage-dependence of transient current steady-state inactivation by - 18.7 +/- 5.9 mV (mean +/- s.e.mean, n = 4). 5 In current-clamp, benzocaine (250 mu M) could block subthreshold, voltage-dependent inward current, increasing the threshold for eliciting action potentials, without preventing their generation (n = 2). 6 Block of late Na+ current by systemic local anaesthetic may play a part in preventing ectopic impulse generation in sensory neurones.